Minors at contexts risk at the edge of the infringement. Sport practice as a preventive proposal

[EN] Just a few miles away from our country (Spain), there is a concentration of children in a poor context and in very deprived conditions showing the body of today. We refer to the north of a neighboring continent, a population that has shown us , once again, the difficulties to get out of that loop called underdevelopment. Therefore, to compare the behavior of children in both countries could be made, especially since our Western view leads us to classify people by their actions. So it is easier to consider any child that exceeds its freedom as to what the legal and political framework are permitting as infringing. But our vision is different, the context to which this group is exposed is more than slightly dangerous and get these children include a classification somewhat tedious to have suffered irremediable situation - without desiring them - would be unfair. And even though it is not an easy path, our experience with the sport as safe conduct towards improving behavior and empowering emotions, making us reconsider the possible resources to work with this group as noted in our days[ES] A tan solo unos kilómetros de distancia de nuestro país (España), existe una concentración de menores en un contexto precario y en condiciones muy desfavorecidas que muestra el ente de nuestros días. Nos referimos al norte de un continente vecino, a una población que nos ha mostrado, una vez más, las dificultades existentes para poder salir de ese bucle llamado subdesarrollo. Por ello, comparar el comportamiento de los menores en ambos países podría hacerse, sobre todo porque nuestra visión occidental nos lleva a clasificar a las personas por sus actos. Así que es más fácil considerar a todo menor que excede su libertad en cuanto a lo que el marco jurídico y político se lo permite como infractor. Pero nuestra visión es distinta, el contexto ante el que se expone este colectivo es algo más que ligeramente peligroso y conseguir englobar a estos menores en una clasificación un tanto tediosa para la situación irremediable que han sufrido -sin ellos desearla-, sería injusto. Y a pesar de que no se trate de un camino fácil, nuestra experiencia mediante la práctica deportiva, como salvoconducto hacia una mejora de la conducta y la potenciación de emociones, nos hizo recapacitar sobre los posibles recursos para trabajar con este colectivo tan señalado en nuestros días.Carrasco Santos, H.; González González, P.; Gutiérrez Sánchez, JD.; Jiménez Hernández, AS. (2014). Menores en contextos de riesgo al borde de la infracción. La práctica deportiva como propuesta preventiva. Revista sobre la infancia y la adolescencia. (7):2-10. doi:10.4995/reinad.2014.3332SWORD2107Bargach, A, (2009). La integración del menor migrante sin referente adulto en el país receptor. En Jiménez, A. (Coord.), Menores migrantes sin referentes familiares. Una perspectiva integral del fenómeno. Granada: Grupo Editorial Universitario.Muriel. A, et al. (2008). Los programas deportivos en los centros penitenciarios. Madrid: Ministerio del Interio

Characterization of a Fetal Liver Cell Population Endowed with Long-Term Multiorgan Endothelial Reconstitution Potential.

Stable reconstitution of vascular endothelial beds upon transplantation of progenitor cells represents an important challenge due to the paucity and generally limited integration/expansion potential of most identified vascular related cell subsets. We previously showed that mouse fetal liver (FL) hemato/vascular cells from day 12 of gestation (E12), expressing the Stem Cell Leukaemia (SCL) gene enhancer transgene (SCL-PLAP+ cells), had robust endothelial engraftment potential when transferred to the blood stream of newborns or adult conditioned recipients, compared to the scarce vascular contribution of adult bone marrow cells. However, the specific SCL-PLAP+ hematopoietic or endothelial cell subset responsible for the long-term reconstituting endothelial cell (LTR-EC) activity and its confinement to FL developmental stages remained unknown. Using a busulfan-treated newborn transplantation model, we show that LTR-EC activity is restricted to the SCL-PLAP+ VE-cadherin+ CD45- cell population, devoid of hematopoietic reconstitution activity and largely composed by Lyve1+ endothelial-committed cells. SCL-PLAP+ Ve-cadherin+ CD45- cells contributed to the liver sinusoidal endothelium and also to the heart, kidney and lung microvasculature. LTR-EC activity was detected at different stages of FL development, yet marginal activity was identified in the adult liver, revealing unknown functional differences between fetal and adult liver endothelial/endothelial progenitors. Importantly, the observations that expanding donor-derived vascular grafts colocalize with proliferating hepatocyte-like cells and participate in the systemic circulation, support their functional integration into young livers. These findings offer new insights into the engraftment, phonotypical, and developmental characterization of a novel endothelial/endothelial progenitor cell subtype with multiorgan LTR-EC activity, potentially instrumental for the treatment/genetic correction of vascular diseases. Stem Cells 2017;35:507-521.Spanish Ministry of Economy and Competitiveness (Grant IDs: BFU2010- 15801, CSD-2007-00008), Junta de Andalucıa Regional Government (Grant ID: CVI-295), European Regional Development Funds, Wellcome Trust, Medical Research CouncilThis is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/stem.249

Extracting the infrared permittivity of SiO2 substrates locally by near-field imaging of phonon polaritons in a van der Waals crystal

Layered materials in which individual atomic layers are bonded by weak van der Waals forces (vdW materials) constitute one of the most prominent platforms for materials research. Particularly, polar vdW crystals, such as hexagonal boron nitride (h-BN), alpha-molybdenum trioxide (α-MoO3) or alpha-vanadium pentoxide (α-V2O5), have received significant attention in nano-optics, since they support phonon polaritons (PhPs)―light coupled to lattice vibrations― with strong electromagnetic confinement and low optical losses. Recently, correlative far- and near-field studies of α-MoO3 have been demonstrated as an effective strategy to accurately extract the permittivity of this material. Here, we use this accurately characterized and low-loss polaritonic material to sense its local dielectric environment, namely silica (SiO2), one of the most widespread substrates in nanotechnology. By studying the propagation of PhPs on α-MoO3 flakes with different thicknesses laying on SiO2 substrates via near-field microscopy (s-SNOM), we extract locally the infrared permittivity of SiO2. Our work reveals PhPs nanoimaging as a versatile method for the quantitative characterization of the local optical properties of dielectric substrates, crucial for understanding and predicting the response of nanomaterials and for the future scalability of integrated nanophotonic devices

Deslizamientos submarinos y tsunamis en el Mar de Alborán. Un ejemplo de modelización numérica

Texto científico de carácter divulgativo.Texto científico de carácter divulgativo en el que se presenta un trabajo de modelado matemático y simulación numérica de un hipotético tsunami producido en el Mar de Alborán por un deslizamiento masivo de materiales en el flanco sur de la Dorsal de Alborán.Instituto Español de Oceanografía. Universidad de Málaga

Central Ceramide-Induced Hypothalamic Lipotoxicity and ER Stress Regulate Energy Balance

Hypothalamic endoplasmic reticulum (ER) stress is a key mechanism leading to obesity. Here, we demonstrate that ceramides induce lipotoxicity and hypothalamic ER stress, leading to sympathetic inhibition, reduced brown adipose tissue (BAT) thermogenesis, and weight gain. Genetic overexpression of the chaperone GRP78/BiP (glucoseregulated protein 78 kDa/binding immunoglobulin protein) in the ventromedial nucleus of the hypothalamus (VMH) abolishes ceramide action by reducing hypothalamic ER stress and increasing BAT thermogenesis, which leads to weight loss and improved glucose homeostasis. The pathophysiological relevance of this mechanism is demonstrated in obese Zucker rats, which show increased hypothalamic ceramide levels and ER stress. Overexpression of GRP78 in the VMH of these animals reduced body weight by increasing BAT thermogenesis as well as decreasing leptin and insulin resistance and hepatic steatosis. Overall, these data identify a triangulated signaling network involving central ceramides, hypothalamic lipotoxicity/ER stress, and BAT thermogenesis as a pathophysiological mechanism of obesity

Molecular profiling of long-term responders to immune checkpoint inhibitors in advanced non-small cell lung cancer

Altres ajuts: This work was supported by the Fundacion Cientifica Asociación Española Contra el Cancer-AECC [grant number GCB14142170 to LMM, MS-C, and EF].Immunotherapy has transformed advanced non-small cell lung cancer (NSCLC) treatment strategies and has led to unprecedented long-lasting responses in some patients. However, the molecular determinants driving these long-term responses remain elusive. To address this issue, we performed an integrative analysis of genomic and transcriptomic features of long-term immune checkpoint inhibitors (ICIs)-associated responders. We assembled a cohort of 47 patients with NSCLC receiving ICIs that was enriched in long-term responders [>18 months of progression-free survival (PFS)]. We performed whole-exome sequencing from tumor samples, estimated the tumor mutational burden (TMB), and inferred the somatic copy number alterations (SCNAs). We also obtained gene transcription data for a subset of patients using Nanostring, which we used to assess the tumor immune infiltration status and PD-L1 expression. Our results indicate that there is an association between TMB and benefit to ICIs, which is driven by those patients with long-term response. Additionally, high SCNAs burden is associated with poor response and negatively correlates with the presence of several immune cell types (B cells, natural killers, regulatory T cells or effector CD8 T cells). Also, CD274 (PD-L1) expression is increased in patients with benefit, mainly in those with long-term response. In our cohort, combined assessment of TMB and SCNAs burden enabled identification of long-term responders (considering PFS and overall survival). Notably, the association between TMB, SCNAs burden, and PD-L1 expression with the outcomes of ICIs treatment was validated in two public datasets of ICI-treated patients with NSCLC. Thus, our data indicate that TMB is associated with long-term benefit following ICIs treatment in NSCLC and that TMB, SCNAs burden, and PD-L1 are complementary determinants of response to ICIs

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer

Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa